Co-regulation ofSalmonella entericagenes required for virulence and resistance to antimicrobial peptides by SlyA and PhoP/PhoQ.

Analysis of the transcriptome ofslyAmutantSalmonella entericaserovar Typhimurium revealed that many SlyA-dependent genes, includingpagC,pagD,ugtL,mig-14,virK,phoN,pgtE,pipB2,sopD2,pagJandpagK, are also controlled by the PhoP/PhoQ regulatory system. Many SlyA- and PhoP/PhoQ-co-regulated genes have functions associated with the bacterial envelope, and some have been directly implicated in virulence and resistance to antimicrobial peptides. Purified His-tagged SlyA binds to thepagCandmig-14promoters in regions homologous to a previously proposed‘SlyA-box’. ThepagCpromoter lacks a consensus PhoP binding site and does not bind PhoPin vitro, suggesting that the effect of PhoP onpagCtranscription is indirect. Stimulation ofpagCexpression by PhoP requires SlyA. Levels of SlyA protein and mRNA are not significantly changed under low-magnesium PhoP-inducing conditions in whichpagCexpression is profoundly elevated, however, indicating that the PhoP/PhoQ system does not activatepagCexpression by altering SlyA protein concentration. Models are proposed in which PhoP may control SlyA activity via a soluble ligand or SlyA may function as an anti-repressor to allow PhoP activation. The absence of almost all SlyA-activated genes from theEscherichia coliK12 genome suggests that the functional linkage between the SlyA and PhoP/PhoQ regulatory systems arose asSalmonellaevolved its distinctive pathogenic lifestyle. [ABSTRACT FROM AUTHOR]